The overall aim of our research proposal is to investigate the extent to which pharmacological agents can restore useful visual function to cats with experimentally produced amblyopia. Numerous observations indicate that abnormal inhibitory mechanisms play a role in amblyopic visual deficits and that disinhibition can alleviate these deficits. Our rational is to determine to what extent pharmacological disinhibition, by antagonism of known inhibitory neurotransmitters, can reverse amblyopic deficits as determined neurophysiologically in visual cortex and the lateral geniculate nucleus (LGN) and behavorially in formal testing of visual acuity. We will concentrate on detailed studies of two pharmcological agents which we have found effective: bicuculline (a GABA antagonist) and naloxone (an antagonist of the opiates and GABA). The proposed electrophysiological studies involve comparisons of the responses of single cells to visual stimulation before and after administration of pharmacological agents (applied both intravenously and by microiontophoresis). Our goals are to 1) define the anatomical locus of the abnormal inhibition which produces physiological deficits in cells driven by an amblyopic eye, 2) to determine whether there are single or multiple inhibitory mechanisms involved, 3) to compare inhibitory processes in visual cortex and LGN, and 4) to compare the role of abnormal inhibition in animal models of deprivation amblyopia (where there is an anatomical loss of input) with models of strabismic amblyopia (where there is not a loss of input). The behavioral studies involve comparisons of the visual acuity of the normal and amblyopic eye before and after intravenous administration of pharmacological agents. Our aims are to determine 1) whether there are differences in the extent of behavioral recovery in animal models of deprivation and strabismic amblyopia and 2) whether long lasting behavioral improvements can be achieved through a combination of chronic drug administration and forced usage of the amblyopic eye. These studies bear on our understanding of how abnormal experience impairs brain function and also directly address the potential for reversal of these impairments.